In 16 experiments on 4 healthy subjects, the effect of procedures which alter blood glucose, ie, infusion of 0.2 units/kg body wt/hr insulin and/or 0.66 g/kg body wt/hr glucose, on gastric acid secretion, plasma gastrin, and plasma osmolality was studied, Each subject underwent four different experimental procedures, each lasting 4 hr. All had in common one basal hour and the infusion of insulin in the second hour, but differed in the time of infusion of glucose or isotonic saline. To control for order effects, the four procedures were applied to the subjects in the form of a Latin square. Acid output was measured continuously be means of intragastric titration and a telemetering capsule; blood glucose, plasma gastrin, and plasma osmolaity were determined in 15-min intervals. An inverse relationship between blood glucose and acid output was found: Low glucose levels were associated with high rates of acid secretion, high glucose levels with low acid secretion. No noticeable changes occurred in either plasma gastrin or plasma osmolality. These results reveal a determining influence of blood glucose levels on acid secretion. On the basis of earlier work in animals it is concluded that this influence is exerted via the reciprocal activities of the hypothalamic satiety and feeding centers.